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Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

We derived a new method for direct calculation of the modal contributions to thermal conductivity, which is termed Green-Kubo modal analysis (GKMA). The GKMA method combines the lattice dynamics formalism with the Green-Kubo formula for thermal conductivity, such that the thermal conductivity becomes a direct summation of modal contributions, where one need not define the phonon velocity. As a result, the GKMA method can be applied to any material group of atoms, where the atoms vibrate around stable equilibrium positions, which includes non-stoichiometric compounds, random alloys, amorphous materials and even rigid molecules. By using molecular dynamics simulations to obtain the time history of each mode's contribution to the heat current, one naturally includes anharmonicity to full order and can obtain insight into the interactions between different modes through the cross-correlations. As an example, we applied the GMKA method to crystalline and amorphous silicon. The modal contributions at each frequency result from the analysis and thereby allow one to apply a quantum correction to the mode heat capacity to determine the temperature dependence of thermal conductivity. The predicted temperature dependent thermal conductivity for amorphous silicon shows the best agreement with experiments to date. The GKMA method provides new insight into the nature of phonon transport, as it casts the problem in terms of mode-mode correlation instead of scattering, and provides a general unified formalism that can be used to understand phonon-phonon interactions in essentially any class of materials or structures where the atoms vibrate around stable equilibrium sites.

Background Acer pseudosieboldianum (Pax) Komarov, is a colorful leaf species belonging to the family Aceraceae, mainly distributed in Northeast China, Russia, and northern Korea. The leaves of Acer pseudosieboldianum are green in spring and summer, and turning red in autumn, which is of high ornamental value. In previous study, a mutant maple was selected with alternating red-green leaf color in spring and summer. However, the reason for the color mutation was not clear. Therefore, UPLC /LC-MS and RNA-seq were used to analyze the anthocyanin components and related differentially expressed genes in the spring leaf color changes of A. pseudosieboldianum mutant, which can provide broader insights into the complex coloration process of leaf color. Results The results showed that the mutant leaves contained a total of 50 anthocyanin metabolites. In all differential metabolites of anthocyanins, Cyanidin-3,5-O-diglucoside, Cyanidin-3-O-glucoside, Cyanidin-3-O-sambubioside not only had higher content, but also showed significant changes at different stages. Especially, the consistent high content of anthocyanins in Cyanidin-3-O-glucoside, which are the main pigments for leaf color. In addition, 11,522 genes were found to be significantly differentially with 5,477 genes up-regulated, and 6,045 genes down-regulated. We identified relevant information for differentially expressed genes (DEGs) associated with leaf color, including 20 structural genes involved in anthocyanin biosynthesis, 12 transcription factors, and eight genes related to anthocyanin transport. Conclusions Among all anthocyanins of A. pseudosieboldianum mutant leaf, Cyanidin-3-O-glucoside remained high in all three stages of leaves, which is main substances for the leaf color. Additionally, 20 structure gene, 12 transcription factors and some genes associated with anthocyanin synthesis and transport were screened and there was a complex metabolic network in mutant leaves. This study provided a basis for resource innovation and landscaping applications of Acer plants by analyzing the anthocyanin metabolites and expression of DEGs in the leaf coloring process.

Ether based electrolytes have surfaced as alternatives to conventional carbonates allowing for enhanced electrochemical performance of sodium-ion batteries; however, the primary source of the improvement remains poorly understood. Here we show that coupling titanium dioxide and other anode materials with diglyme does enable higher efficiency and reversible capacity than those for the combination involving ester electrolytes. Importantly, the electrolyte dependent performance is revealed to be the result of the different structural evolution induced by a varied sodiation depth. A suit of characterizations show that the energy barrier to charge transfer at the interface between electrolyte and electrode is the factor that dominates the interfacial electrochemical characteristics and therefore the energy storage properties. Our study proposes a reliable parameter to assess the intricate sodiation dynamics in sodium-ion batteries and could guide the design of aprotic electrolytes for next generation rechargeable batteries. Sodium ion batteries are known to benefit from the use of ether electrolytes. Here the authors reveal the origin showing that the energy barrier of charge transfer at the electrolyte/electrode interface dominates the interfacial electrochemical characteristics and is favorably small.

High-voltage lithium metal batteries suffer from poor cycling stability caused by the detrimental effect on the cathode of the water moisture present in the non-aqueous liquid electrolyte solution, especially at high operating temperatures (e.g., ≥60 °C). To circumvent this issue, here we report lithium hexamethyldisilazide (LiHMDS) as an electrolyte additive. We demonstrate that the addition of a 0.6 wt% of LiHMDS in a typical fluorine-containing carbonate-based non-aqueous electrolyte solution enables a stable Li||LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811) coin cell operation up to 1000 or 500 cycles applying a high cut-off cell voltage of 4.5 V in the 25 °C−60 °C temperature range. The LiHMDS acts as a scavenger for hydrofluoric acid and water and facilitates the formation of an (electro)chemical robust cathode|electrolyte interphase (CEI). The LiHMDS-derived CEI prevents the Ni dissolution of NCM811, mitigates the irreversible phase transformation from layered structure to rock-salt phase and suppresses the side reactions with the electrolyte solution. High-voltage non-aqueous lithium metal batteries suffer from poor cycling stability due to the presence of impurities in the electrolyte solution. Here, the authors report lithium hexamethyldisilazide to scavenge HF and H 2 O, prevent the Ni dissolution and suppress side reactions during cycling.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with extremely skewed ethnic and geographic distributions. Increasing evidence indicates that targeting the tumor microenvironment (TME) represents a promising therapeutic approach in NPC, highlighting an urgent need to deepen the understanding of the complex NPC TME. Here, we generated single-cell transcriptome profiles for 7581 malignant cells and 40,285 immune cells from fifteen primary NPC tumors and one normal sample. We revealed malignant signatures capturing intratumoral transcriptional heterogeneity and predicting aggressiveness of malignant cells. Diverse immune cell subtypes were identified, including novel subtypes such as CLEC9A + dendritic cells (DCs). We further revealed transcriptional regulators underlying immune cell diversity, and cell–cell interaction analyses highlighted promising immunotherapeutic targets in NPC. Moreover, we established the immune subtype-specific signatures, and demonstrated that the signatures of macrophages, plasmacytoid dendritic cells (pDCs), CLEC9A + DCs, natural killer (NK) cells, and plasma cells were significantly associated with improved survival outcomes in NPC. Taken together, our findings represent a unique resource providing in-depth insights into the cellular heterogeneity of NPC TME and highlight potential biomarkers for anticancer treatment and risk stratification, laying a new foundation for precision therapies in NPC.

The idea of treating phonon transport as equivalent to transport through a gas of particles is termed the phonon gas model (PGM), and it has been used almost ubiquitously to try and understand heat conduction in all solids. However, most of the modes in disordered materials do not propagate and thus may contribute to heat conduction in a fundamentally different way than is described by the PGM. From a practical perspective, the problem with trying to apply the PGM to amorphous materials is the fact that one cannot rigorously define the phonon velocities for non-propagating modes, since there is no periodicity. Here, we tested the validity of the PGM for amorphous materials by assuming the PGM is applicable, and then, using a combination of lattice dynamics, molecular dynamics (MD) and experimental thermal conductivity data, we back-calculated the phonon velocities for the vibrational modes. The results of this approach show that if the PGM was valid, a large number of the mid and high frequency modes would have to have either imaginary or extremely high velocities to reproduce the experimental thermal conductivity data. Furthermore, the results of MD based relaxation time calculations suggest that in amorphous materials there is little, if any, connection between relaxation times and thermal conductivity. This then strongly suggests that the PGM is inapplicable to amorphous solids.

Patients with locoregionally advanced nasopharyngeal carcinoma have a high risk of disease relapse, despite a high proportion of patients attaining complete clinical remission after receiving standard-of-care treatment (ie, definitive concurrent chemoradiotherapy with or without induction chemotherapy). Additional adjuvant therapies are needed to further reduce the risk of recurrence and death. However, the benefit of adjuvant chemotherapy for nasopharyngeal carcinoma remains controversial, highlighting the need for more effective adjuvant treatment options. This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was done at 14 hospitals in China. Patients (aged 18–65 years) with histologically confirmed, high-risk locoregionally advanced nasopharyngeal carcinoma (stage III–IVA, excluding T3–4N0 and T3N1 disease), no locoregional disease or distant metastasis after definitive chemoradiotherapy, an Eastern Cooperative Oncology Group performance status of 0 or 1, sufficient haematological, renal, and hepatic function, and who had received their final radiotherapy dose 12–16 weeks before randomisation, were randomly assigned (1:1) to receive either oral metronomic capecitabine (650 mg/m2 body surface area twice daily for 1 year; metronomic capecitabine group) or observation (standard therapy group). Randomisation was done with a computer-generated sequence (block size of four), stratified by trial centre and receipt of induction chemotherapy (yes or no). The primary endpoint was failure-free survival, defined as the time from randomisation to disease recurrence (distant metastasis or locoregional recurrence) or death due to any cause, in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of capecitabine or who had commenced observation. This trial is registered with ClinicalTrials.gov, NCT02958111. Between Jan 25, 2017, and Oct 25, 2018, 675 patients were screened, of whom 406 were enrolled and randomly assigned to the metronomic capecitabine group (n=204) or to the standard therapy group (n=202). After a median follow-up of 38 months (IQR 33–42), there were 29 (14%) events of recurrence or death in the metronomic capecitabine group and 53 (26%) events of recurrence or death in the standard therapy group. Failure-free survival at 3 years was significantly higher in the metronomic capecitabine group (85·3% [95% CI 80·4–90·6]) than in the standard therapy group (75·7% [69·9–81·9]), with a stratified hazard ratio of 0·50 (95% CI 0·32–0·79; p=0·0023). Grade 3 adverse events were reported in 35 (17%) of 201 patients in the metronomic capecitabine group and in 11 (6%) of 200 patients in the standard therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (18 [9%] patients had grade 3 hand-foot syndrome). One (<1%) patient in the metronomic capecitabine group had grade 4 neutropenia. No treatment-related deaths were reported in either group. The addition of metronomic adjuvant capecitabine to chemoradiotherapy significantly improved failure-free survival in patients with high-risk locoregionally advanced nasopharyngeal carcinoma, with a manageable safety profile. These results support a potential role for metronomic chemotherapy as an adjuvant therapy in the treatment of nasopharyngeal carcinoma. The National Natural Science Foundation of China, the Key-Area Research and Development Program of Guangdong Province, the Natural Science Foundation of Guangdong Province, the Innovation Team Development Plan of the Ministry of Education, and the Overseas Expertise Introduction Project for Discipline Innovation. For the Chinese translation of the abstract see Supplementary Materials section.

N 6 -Methyladenosine (m6A), the most abundant internal modification associated with eukaryotic mRNAs, has emerged as a dynamic regulatory mechanism controlling the expression of genes involved in many physiological activities by affecting various steps of mRNA metabolism, including splicing, export, translation, and stability. Here, we review the general role of m6A, highlighting recent advances related to the three major types enzymes that determine the level of m6A modification (i.e., writers, erasers, and readers) and the regulatory mechanism by which m6A influences multiple stages of RNA metabolism. This review clarifies the close connection and interaction between m6A modification and nuclear gene expression, and provides key background information for further studies of its roles in numerous physiological and pathophysiological processes. Among them, perhaps the most eye-catching process is tumorigenesis. Clarifying the molecular mechanism of tumorigenesis, development and metastasis in various tissues of the human body is conducive to curbing out-of-control cell activities from the root and providing a new strategy for human beings to defeat tumors.

A simple and effective method based on in situ infrared spectroscopy and two-dimensional (2D) correlation analysis was applied to research the chemical changes and curing reaction mechanism of epoxy resin and amine curing agents. It is generally agreed that the epoxy groups in epoxy resin react with amino groups to form new C–N and hydroxyl groups during the curing reaction process. However, detailed information about the curing reaction mechanism of epoxy resin and amine curing agents has rarely been reported. In this work, the curing reaction mechanism can be deeply understood from the results of 2D correlation analysis. Due to the nucleophilic addition reaction of amino and epoxy groups, the nitrogen atoms of primary amines easily combine with the carbon atoms in epoxy groups, which forms new C–N groups. Then, the C–O bonds in epoxy groups break; finally, as the N–H bonds in primary amines break, the hydrogen atoms combine with the oxygen atoms to form new hydroxyl groups.In situ infrared spectroscopy and two-dimensional (2D) correlation analysis was applied to research the chemical changes and curing reaction mechanism of epoxy resin and amine curing agents. The curing reaction mechanism can be deeply understood from the results. Due to the nucleophilic addition reaction of amino and epoxy groups, the nitrogen atoms easily combine with the carbon atoms, which forms new C-N groups. Then, the C-O bonds break; finally, as the N-H bonds in primary amines break, the hydrogen atoms combine with the oxygen atoms to form new hydroxyl groups.